Multiscale modeling of actin filaments and crosslinked actin networks
Tamara Bidone (MIT), TaeYoon Kim (), Marco Deriu (), Umberto Morbiducci (), Roger Kamm (MIT)
Mechanics and Physics of Biological Cells
Tue 4:20 - 5:40
Barus-Holley 141
Mechanical stability, response to deformation and locomotion of cells are largely due to molecular mechanisms that act on a network of semiflexible biopolymers known as the cytoskeleton. Given the importance of the cytoskeletal network in determining the mechanical responses of cells, there is an increasing interest in understanding its elastic properties starting from the characteristics of the individual components. In this study, we applied a combination of all-atom Molecular Dynamics simulations, Elastic Network Modeling and Brownian Dynamics simulations to evaluate how the combined modifications in bending and stretching rigidities of the actin filaments, owing to the different molecular conformation for the presence of cations and/or nucleotides, affect strain-stiffening of a cross-linked actin network under constant shear strain deformation. We find that in physiological conditions with typical Mg2+ bound filaments, a reduced filament bending stiffness and an increased extensional stiffness lead to networks that stiffen at lower strains compared to networks of Ca2+ bound filaments. Similarly, networks with filaments bound to ATP are stiffer than networks with filaments bound to ADP. These and other results show that the combined mechanical effects that the bound ligands have on the single filaments can be thought of as a method for cells to efficiently increase or decrease locally the rigidity of its cytoskeleton. For example, at the leading edge of a migrating cell, a higher fraction of actin filaments are bound to ATP with respect to the actin filaments at the trailing edge, thus a stiffer network should be present. Support of the Singapore MIT Alliance for Research and Technology and the MITOR fellowship to TB are greatly acknowledged.